Morphine Titration In Cancer Pain Management

Dose Initiation

• Opioid naive patients: 5 mg 4-hourly of IR oral morphine.
• Patients tolerant to weak opioids (already on regular tramadol or dihydrocodeine): 10 mg 4-hourly 
• Elderly opioid naive patients: starting dose of 2.5 mg 4 - 6 hourly of IR oral morphine (10 - 15 mg in 24 hours)
• Patients receiving IR morphine every 4-hours, a double dose at bedtime is recommended for convenience to prevent being woken up by pain at night. 

Parenteral vs Oral

• SC route is useful for patients unable to tolerate oral opioids. 
• No difference in efficacy or side effects between continuous infusion and intermittent SC opioids 
• Titration can be performed parenterally for rapid onset of analgesia. IV morphine titration gives faster onset of analgesia compared to oral morphine titration.
• SC morphine titration has similar efficacy as IV morphine titration, and both methods are safe and tolerated well.

Breakthrough Pain

• Starting an opioid: use immediate release (IR) until dose is stabilized. Alternatively,some clinicians may choose to start with an oral controlled-release (CR) formulation, with an IR form available for breakthrough pain.
• Opioid naïve patients: start with 2.5 to 5 mg of morphine q4h with breakthrough medication ordered at 1.25 to 2.5 mg of morphine q1h prn. 
• Analgesic effectiveness: reassessed after 24 hours as it takes five half lives to reach a steady state (5 x 4 hrs = 20 hrs). 
• Total all the regular and breakthrough opioid used in the last 24 hours to get the total daily dose (TDD). 
• Divide this amount by the number of doses for the next 24 hours (normally 6=q4h) and give this dose regularly q4h with 10% of the TDD given q1h p.r.n. as a breakthrough/rescue dose (BTD) for breakthrough/rescue pain.
• Dose adjustments: should not be made more frequently than every 24 hours. Also assess for end of dose pain, and the presence of incident pain, which may require further titration. 
• Use IR opioid formulations for breakthrough doses (BTD)and remember to increase the breakthrough dose proportionately when the regular dose is increased.
• When full pain relief is achieved, yet adverse effect have developed, employ a dose reduction to try and maintain adequate pain control with diminished adverse effects. 
• Doubling the nightime dose: will avoid wakening the patient in the early morning for a scheduled q4h dose, however, night loading doses should be considered only for patients with good pain control.

Sustained Release Formulation

• The use of sustained release opioids appears to be a better dosing strategy.
• When good pain control is achieved with a stable dose with an immediate release formulation, consider use of a long acting product to improve compliance.
• When the patient is on sustained release opioids or fentanyl patches it is usual to titrate the dose every 48 and 72 hours respectively. 
• If fentanyl is used, total the amount of breakthrough opioid analgesic given in the last 24 hours and convert that amount to an additional equivalent size fentanyl patch. If titration is done frequently switch to a short acting preparation. 
• Rapidly escalating or pain is requiring frequent titration: use short acting opioids q4h until pain is controlled and opioid needs are stabilized. 
• Consider development of tolerance (which may require opioid rotation) or reassessment for a new or progressive medical problem. 
• When patients are elderly or frail, titrate over a number of days rather than rapidly over 1 to 2 days.For severe pain the rate of titration may need to be more aggressive.

Increase strength of PRN dose  

• If pain control is inadequate after 3 PRN doses with no evidence of morphine toxicity increase the PRN dose by 2.5-5mg. 
• If pain control remains inadequate after 3 more PRN doses, further dose increases can be made (30-50% of previous PRN dose).

REFERENCE:

CPG Management Of Cancer Pain 2010

European Society For Medical Oncology Guideline 2011

Principles Of Opiod Management:https://www.fraserhealth.ca/media/16FHSymptomGuidelinesOpioid.pdf